Universität zu Köln

Rangaraju, Sunitha, Solis, Gregory M., Thompson, Ryan C., Gomez-Amaro, Rafael L., Kurian, Leo ORCID: 0000-0001-7466-5169, Encalada, Sandra E., Niculescu, Alexander B., III, Salomon, Daniel R. and Petrascheck, Michael ORCID: 0000-0002-1010-145X (2015). Suppression of transcriptional drift extends C-elegans lifespan by postponing the onset of mortality. eLife, 4. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Longevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions. These changes cause a transcriptome-wide loss in mRNA stoichiometry and loss of co-expression patterns in aging animals, as compared to young adults. Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rangaraju, Sunitha UNSPECIFIED UNSPECIFIED UNSPECIFIED Solis, Gregory M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thompson, Ryan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gomez-Amaro, Rafael L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurian, Leo UNSPECIFIED orcid.org/0000-0001-7466-5169 UNSPECIFIED Encalada, Sandra E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niculescu, Alexander B., III UNSPECIFIED UNSPECIFIED UNSPECIFIED Salomon, Daniel R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Petrascheck, Michael UNSPECIFIED orcid.org/0000-0002-1010-145X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-385913
DOI:	10.7554/eLife.08833
Journal or Publication Title:	eLife
Volume:	4
Date:	2015
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION PROFILES; HEAT-SHOCK RESPONSE; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; DNA-DAMAGE; LONGEVITY; STRESS; PROTEOSTASIS; HEALTHSPAN; DEFECTS Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38591